For the biology nerds in the group, here’s some interesting work on how obesity functions as an inflammatory state. The basic premise, as I’ve indicated in previous posts, is that a “critical mass” (if you will) of adipose tissue produces a particular hormonal environment, because fat tissue is hormonally active.
In obesity, write the authors, “excess adipose tissue accumulation is accompanied by local inflammation, characterized by infiltration of inflammatory cells and by elevated production of proinflammatory cytokines, jointly activating inflammatory pathways in adipocytes… [T]he consequent alteration in the composition of secreted products from adipocytes contributes to both local and systemic insulin resistance. Particularly, liver insulin sensitivity can be impaired by obesity-induced alterations in adipokine secretion and by elevation in fat tissue–derived cytokines and fatty acids.” [Translation: more fat equals more inflammation, which creates insulin resistance, particularly in the liver.]
A cellular receptor known as Fas or CD95 is an important player here. Fas, when activated and behaving itself, generates apoptosis — necessary cell death. Normally, this is a good thing. You don’t want diseased or dysfunctional cells hanging around. So, apoptosis ensures that the sick and old of the cellular herd are “sent away to live on a farm”. It’s like nature’s housekeeper.
But sometimes Fas can be a naughty little monkey and “induce non-apoptotic signalling pathways”. It can stimulate inflammation and consequently insulin resistance. “For example, in different cell lines and tissues, Fas activation was shown to induce secretion of proinflammatory cytokines such as IL-1α, IL-1β, IL-6, IL-8 (KC), and MCP-1, rendering it a potential key component of the inflammatory response… Our findings point toward an important role of adipocyte Fas expression in the development of obesity-associated fat tissue inflammation and insulin resistance.”
In insulin-resistant mice as well as obese and diabetic patients, Fas expression is increased. F-A-S spells B-A-D. On the other hand, mice genetically altered not to have Fas are protected against this obesity-induced insulin resistance, which includes protection against liver steatosis (fatty liver, which is a less-known yet potentially more damaging element of metabolic syndrome).
This suggests that there may be treatments in future that address the Fas expression. At the very least it offers new understanding of the relationship between obesity, inflammation, and associated consequences.